The invention relates to a method for determining the concentration of sugar in the presence of foreign substances, in particular for the determination of glucose in a body fluid. This is accomplished by means of a device which includes a test electrode with a membrane placed in front of it the electrode being contained in an electrocatalytic sugar sensor, whereby the test electrode is set to a reactivation potential and to a test potential and whereby the current flowing during the test period--after a time delay with reference to the beginning of the test period--is evaluated as a test signal.
The determination of the concentration of sugar in a body fluid, particularly in a patient's blood, is significant, for example, to diagnose or evaluate diabetics. For a diabetic patient, whose natural regulation of body glucose is disturbed, it is thus important that the normal blood glucose level as artificially maintained to be as constant as possible over the course of the day. The blood glucose level can be influenced by diet, insulin injections and by physical therapy. It is essential in this regard that an overcompensation or an undercompensation of the sugar content in the blood be avoided. A patient himself, must be aware of the blood sugar content to be able to use appropriate measures as necessary for control of his or her sugar levels.
The automatic regulation of the glucose concentration by means of an artificial Beta cell has been considered, whereby the insulin supply to the blood is controlled by a glucose sensor such that whenever a deviation occurs from an ideal glucose level insulin is introduced into the blood in proportion to the deviation from the ideal level.
Until now glucose determination in the blood has been measured, in general, externally in the laboratory by photometric methods. There are, however, also electrochemical sensors that provide a direct determination of the glucose in the body fluid. In these so-called enzyme sensors, the glucose is oxidized with the aid of glucose oxidase into gluconic acid, such that oxygen is consumed and hydrogen peroxide is formed. The consumption of oxygen as well as the hydrogen peroxide formation can be electrochemically measured and thus a signal can be obtained that is related to the concentration of glucose. Since enzyme sensors operate selectively and do not react to foreign substances, a reproducible determination of glucose is possible. However, such sensors do not lend themselves to long-term implantation, because the enzymes, as any other proteins, decay over time under physiological conditions, i.e. they do not have long-term stability when introduced into a human body.
An electrocatalytic glucose sensor has been made known through British Pat. No. 1,422,172. This sensor, when operated in a voltage control mode, is however not stable over long term; whereas, on the other hand, when operated in a current control mode the sensitivity does not achieve a desired accuracy.
With electrocatalytic glucose sensors intermittent measurements over time are possible, especially relative measurements (cf. "Trans. Amer. Soc. Artif. Int. Organs", Vol. XIX, 1973, pp 352-360). However, disturbances of the test signal by coreactants always occur. Impurities can be oxidized at the test electrode thereby providing an inaccurate test signal or can reduce the activity of the test electrode by blocking. With implantable sensors, components of body fluids, especially urea and amino acids, have exhibited interference, preventing the generation of reproducible, long-term measurements.
The above shortcomings also apply to an implantable electrocatalytic glucose sensor such as the one described in the journal "Biomed Technik", 22 (1977), Supplement Volume, pp 399-400. This sensor, which has a test electrode, a counter electrode, and a reference electrode, is driven by the so called potential step method, i.e. the test electrode has alternately applied to it a test potential and a reactivation potential which is more positive with reference to the test potential. During the test period the current is integrated and the integral thus obtained represents the test signal at the end of the test period.
A sensitive and reliable glucose determination, even in body fluids, involves the method published in U.S. Pat. No. 4,366,033 in which the evaluation of the current after a time delay with respect to the beginning of the test period is undertaken and in which a membrane, placed in front of the test electrode of the electrocatalytic sugar sensor, impedes the supply of interfering foreign substances to the test electrode in such a way that a diffusion limiting current is set up in the reactivation phase upon oxidation of the foreign substances. A reliable determination of the glucose concentration over a longer period of time turns out to be difficult if varying concentrations of urea are present in the body fluid. Then the glucose test signal can be relatively strongly influenced such that significant errors occur in the glucose determination. However, in a continuous blood sugar determination varying concentrations of urea must always be taken into consideration.